Ortho-quinone methides are reactive intermediates with wide ranging applications in organic synthesis. However, their propensity to rearomatize renders them transitory and reactive, which has made their implementation in organic synthesis challenging. An asymmetric and organocatalytic multicomponent reaction platform was developed to address this challenge by accessing ortho-quinone methide intermediates in situ through a Friedel-Crafts hydroxy-alkylation condensation of phenols, aldehydes, and boronates. This approach provided a practical and general method to access to chiral di- and triaryl methane products in high yields and enantioselectivities from commercially available starting materials. An unanticipated cyclization pathway was discovered while exploring the scope of the reaction that afforded 2,4-diarylchroman products from an electron rich styrenyl boronate. Reaction conditions were optimized to select for the cyclization pathway, which afforded chroman products with high levels of enantio- and diastereoselectivity.
The myristinin natural products are DNA polymerase-β inhibitors and DNA-damaging agents that contain a privileged chroman scaffold within their core. The multicomponent cyclization strategy was applied towards the synthesis of the myristinin natural products without success. To circumvent issues with reactivity, the multicomponent reaction platform was extended to an intermolecular cycloaddition of in situ generated ortho-quinone methides from phenols, aldehydes, and styrenes to provide 2,4-diarylchromans. The core of myristinins B/C was synthesized using the multicomponent cycloaddition strategy providing high yield and diastereoselectivity with remarkable step economy. An enantioselective version of the multicomponent cycloaddition reaction was developed utilizing triisopropyl borate Lewis acid and a chiral biphenol. / 2018-06-21T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/17059 |
| Date | 21 June 2016 |
| Creators | Barbato, Keith Steven |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
Page generated in 0.0019 seconds